PET imaging of synaptic density in Parkinsonian disorders

Abstract

Synaptic dysfunction and altered synaptic pruning are present in people with Parkinsonian disorders. Dopamine loss and alpha‐synuclein accumulation, two hallmarks of Parkinson's disease (PD) pathology, contribute to synaptic dysfunction and reduced synaptic density in PD. Atypical Parkinsonian disorders are likely to have unique spatiotemporal patterns of synaptic density, differentiating them from PD. Therefore, quantification of synaptic density has the potential to support diagnoses, monitor disease progression, and treatment efficacy. Novel radiotracers for positron emission tomography which target the presynaptic vesicle protein SV2A have been developed to quantify presynaptic density. The radiotracers have successfully investigated synaptic density in preclinical models of PD and people with Parkinsonian disorders. Therefore, this review will summarize the preclinical and clinical utilization of SV2A radiotracers in people with Parkinsonian disorders. We will evaluate how SV2A abundance is associated with other imaging modalities and the considerations for interpreting SV2A in Parkinsonian pathology.

GMP-compliant automated radiosynthesis of [18F] SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

“…Thus, in vivo visualization and quantitative analysis of synaptic density offer extensive clinical applications in the diagnosis, treatment monitoring, and mechanistic research of neurological and psychiatric disorders as well as tumors like NED in NETs (Cai et al, 2019). Up to now, Positron emission tomography (PET) imaging of SV2A has a tremendous potential to be utilized as an early-stage biomarker for Alzheimer's disease (AD) (Mecca et al, 2020) (Mecca et al, 2022), Parkinson's disease (PD) (Delva et al, 2020) (Martin et al, 2023), epilepsy (Tang et al, 2022), autism (Bourgeron, 2015), stroke (Michiels et al, 2023) (Michiels et al, 2022), traumatic brain injury (Jamjoom et al, 2021) and Spinocerebellar Ataxia Type 3 (Chen et al, 2023), as well as psychiatric disorders such as schizophrenia and depression in human subjects (Holmes et al, 2019), including In order to conduct a broader and more in-depth investigation into clinical diseases related to SV2A expression, developing a safe and stable multi-dose [ 18 F] SynVesT-1 radioactive imaging agent production process is of great signi cance. Kenneth Dahl and the co-workers had fully automated radiosynthesis of [ 18 F] SynVesT-1, which performed according to good manufacturing procedure (GMP) using a commercially available module (TracerMaker, ScanSys Laboratorieteknik ApS, Copenhagen, Denmark) with minor changes, and result a highyield, acceptance criteria and quality control (Dahl et al, 2022).…”